Did you know that premature, accelerated atherosclerosis may associate chronic inflammatory polyarthritis?

Compared to the healthy population, chronic inflammatory polyarthritis (rheumatoid arthritis RA) patients have increased (2-3x) morbidity and mortality; the majority of which being cardiovascular (CV) disease associated with early accelerated atherosclerosis. The increased CV risk of RA is maintained even after controlling for traditional risk factors, such as smoking and diabetes. Atherosclerosis correlates with the level of systemic inflammatory activity, thus the inflammatory process affects CV morbidity and mortality and accelerated coronary and extra-coronary atherosclerosis.

Atherosclerosis and its obliterative consequences: myocardial infarction, cerebrovascular disease, and peripheral arterial disease result in organ damage, so diagnosis of atherosclerosis in the early, symptom-free preclinical stage is necessary. Nowadays, non-invasive imaging methods are available to determine the preclinical disease, endothelial dysfunction; the ratio of intima media thickness of the carotis artery (IMT) is characterized by brachial artery’s flow mediated dilatation (FMD), and stiffness of the artery wall is assessed by pulse wave velocity (PWV).

Traditional risk factors of atherosclerosis are cigarette smoking, high cholesterol level, hypertension, hyperglycaemia (insulin resistance), diabetes, metabolic syndromes, and overweight/obesity. Unfavourable diet and excessive physical activity may also have a pro-atherogenic effect. Recently, autoimmune rheumatic diseases have been implicated in the development of premature vascular damage; actors of the autoimmune systemic inflammation (inflammatory cells, cytokines, chemokines, proteases, autoantibodies, adhesion molecules etc.) also play a role in the atherothrombotic process associated with autoimmune rheumatic diseases.

Tumour necrosis factor (TNF) is an inflammatory cytokine that favours the inflammatory responses involved in the pathogenesis of RA. It also promotes dyslipidaemia and insulin resistance, upregulates adhesion molecules, leads to formation of fatty streaks, plaque rupture and promotes thrombophilia by encouraging thrombotic events. IL 6 is a pivotal inflammatory cytokine that is not involved in the pathogenesis of RA, but also in many aspects of cardiovascular disease. It has an important role in the first phase of atherosclerosis, as it leads to endothelial damage and stimulates acute phase proteins, such as C-reactive protein (CRP) to provoke plaque formation. 

Regarding prevention and therapy of accelerated atherosclerosis, traditional vascular protection, using statins, ACE inhibitors and aspirin, should also be applied in rheumatoid arthritis. Non-steroidal anti-inflammatory drugs and glucocorticoids do have beneficial effects, despite their atherogenic character. Traditional and biological disease modifying therapies have significant vascular and metabolic effects. Anti-TNF biologics have a favourable effect on lipid profiles; anti-IL6 antagonists and the new JAK signal inhibitors repair endothelial dysfunction and promote regeneration of the artery wall.

In summary, any of the anti-inflammatory therapies, like biologics, by decreasing inflammatory activity, decrease cardiovascular risk and lead to better outcomes in RA patients.